Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin
Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin
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DOI：
10.1016/j.brainres.2015.05.012
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发表时间：
2015-09
期刊：
影响因子：
2.9
通讯作者：
Hideaki Yamamoto;K. Mandai;D. Konno;T. Maruo;F. Matsuzaki;Y. Takai
中科院分区：
文献类型：
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作者：
Hideaki Yamamoto;K. Mandai;D. Konno;T. Maruo;F. Matsuzaki;Y. Takai
对人类大脑畸形（如无脑畸形和双皮质）的研究揭示了神经元迁移在皮质发育过程中的重要性。Afadin是一种膜支架蛋白，调节粘附连接（AJs）的形成和细胞迁移以形成和维持组织结构。在这里，我们报告说，小鼠背侧端脑特异性消融法丁烯表现出类似于人类双皮质，其中异位皮质位于下方的正常运动皮质的缺陷。突变小鼠的正常活动皮层排列方式与对照小鼠相似，而异位皮层则排列紊乱。正如在人类患者中所见，突变小鼠的双皮质是由皮质发育期间受损的神经元迁移形成的。胚胎大脑皮层的afadin基因消融破坏了放射状胶质细胞的AJs，可能导致心尖端足从脑室表面缩回，放射状胶质细胞从脑室区分散到脑室下区和中间区。这些结果表明，afadin是维持放射状胶质细胞AJs所必需的，AJs的破坏可能会导致神经元迁移的异常放射状支架。相反，放射状胶质细胞的增殖或分化没有受到显着影响。综上所述，这些发现表明，afadin是维持神经元迁移的放射状胶质支架所必需的，并且afadin的基因消融导致双皮质的形成。
Studies of human brain malformations, such as lissencephaly and double cortex, have revealed the importance of neuronal migration during cortical development. Afadin, a membrane scaffolding protein, regulates the formation of adherens junctions (AJs) and cell migration to form and maintain tissue structures. Here, we report that mice with dorsal telencephalon-specific ablation ofafadingene exhibited defects similar to human double cortex, in which the heterotopic cortex was located underneath the normotopic cortex. The normotopic cortex of the mutant mice was arranged in the pattern similar to the cortex of the control mice, while the heterotopic cortex was disorganized. As seen in human patients, double cortex in the mutant mice was formed by impaired neuronal migration during cortical development. Genetic ablation ofafadinin the embryonic cerebral cortex disrupted AJs of radial glial cells, likely resulting in the retraction of the apical endfeet from the ventricular surface and the dispersion of radial glial cells from the ventricular zone to the subventricular and intermediate zones. These results indicate that afadin is required for the maintenance of AJs of radial glial cells and that the disruption of AJs might cause an abnormal radial scaffold for neuronal migration. In contrast, the proliferation or differentiation of radial glial cells was not significantly affected. Taken together, these findings indicate that afadin is required for the maintenance of the radial glial scaffold for neuronal migration and that the genetic ablation ofafadinleads to the formation of double cortex.